Diabetic retinopathy (DR) is a major cause of visual loss in diabetic individuals that presents a significant diagnostic challenge. Advances in preventing vision loss in these individuals are hindered by limited understanding of mechanisms underlying DR and the altered relationships between the retinal neural tissue and retinal vasculature. Therefore, an objective test for the early diagnosis and evaluation of DR treatment is certainly needed in order to identify the individuals at great risk for vision-threatening problems. Our goal is to prevent visual loss in diabetic patients with an advanced imaging technique, Doppler Fourier Domain Optical Coherence Tomography (Doppler FD-OCT) that can facilitate a better understanding of the underlying sight- threatening complications of DR and the altered relationships between the neural retina and blood vessels. Our objective is to test the hypothesis that retinal structure alteration precedes disturbances in retinal hemodynamics and visual function deficit in DR. We will accomplish the following aims: Aim 1: Test the hypothesis the diagnostic power of the combination of advanced Doppler FD-OCT imaging and novel quantitative functional-anatomical measures can provide an objective methodology for non-invasive and in vivo quantification of retinal hemodynamics and structure morphology in normal healthy subjects and diabetic patients with and without DR. Aim 2: Test the hypothesis that retinal structure alteration precedes disturbances in retinal hemodynamics and visual function deficit in DR. Our hypothesis predicts that retinal structure alteration precedes disturbance of retinal hemodynamics, and at each stage of progressive DR the magnitude of structure deterioration will be larger than the magnitude of hemodynamic disturbance and visual function deficit. We will define the ratio of dysfunction to retinal structure alterations and hemodynamic disturbances at different stages of retinopathy by comparing anatomical variables, hemodynamic parameters and visual function measures. Our results will provide quantitative information about retinal blood flow in diabetic patients with and without retinopathy, and will improve the early diagnosis and treatment of DR. Our expected outcome will be to facilitate a ratio of visual dysfunction to retinal structure alterations and hemodynamic disturbances at different stages of retinopathy. We will characterize the retinal structure and hemodynamic parameters and relate the findings to systemic measures of control and complications in defined stratified groups of diabetic patients with varying levels of DR. Our impact will influence clinical practice by providing a means of identifying better clinical endpoints for DR clinical trials that are more sensitive to early disease progression than visual acuity and define the exact role of the blood circulation abnormalities in the DR progression. PUBLIC HEALTH RELEVANCE: Diabetic retinopathy is a major public health concern, and efforts should be focused on its prevention. An understanding of the mechanism of diabetic retinopathy is important for elucidating its pathogenesis for early detection and identification of potential future therapies. It will be helpful for healthcare providers and the public to be able to estimate a person's risk of diabetic retinopathy.